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Regulation of Streptococcus mutans AtlA on the cell surface

变形链球菌 AtlA 对细胞表面的调节

基本信息

批准号：
8836521
负责人：
Sang-Joon Ahn
金额：
$ 11.25万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-09 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8836521
关键词：
Architecture Area Autolysin Autolysis Bacteria Bacterial Adhesins Bacterial Physiology Binding Biogenesis Biological Assay Cell Wall Cell surface Cells Complex Critical Pathways Cytokinesis Cytolysis Data Dental caries Development Disease Management Event Future Health In Vitro Individual Infective endocarditis Libraries Ligands Membrane Proteins Microbial Biofilms Microscopic Modeling Molecular Monitor Mus Operon Oral cavity Organism Pathogenesis Pathway interactions Patient risk Pharmacotherapy Pilot Projects Principal Investigator Process Proteins Proteolytic Processing Regulation Regulatory Pathway Research Role Series Streptococcus gordonii Streptococcus mutans Structure Surface Testing Therapeutic base cellular targeting design driving force in vivo inhibitor/antagonist innovation insight killings mouse model mutant novel oral biofilm oral streptococci protein profiling research study screening therapeutic target tool tooth surface

项目摘要

DESCRIPTION (provided by applicant): Development of a mature biofilm on the tooth surface is an important component of bacterial survival and pathogenesis in the oral cavity. Although over the past years, the complexity of the oral biofilm has been rapidly revealed, understanding how bacteria build up mature pathogenic biofilms in a well- defined way, is still lacking, leading to difficulty in identifying and designing new targets for anti-biofilm therapies. Toward this end, the study of the major Streptococcus mutans autolysin AtlA, shown to be required for biofilm maturation, is a new, but critical pathway for a more complete understanding for biofilm development of this organism. The demonstrated ability of the AtlA pathway to modulate cell surface remodeling is a major driving force for the studies outlined in this proposal, providing a new paradigm for the complex biofilm process particularly as related to the cell surface structure and remodeling process. Under this scope, we will focus our efforts in three interrelated areas. In Specific Aim1, we will elucidate how AtlA is functionally and structurally associated with the cell surface through analysis of repeat domains in the AtlA protein. In the Specific Aim 2, we hypothesize that surface localization and activity of AtlA are modulated primarily by the gene products encoded within the atlA operon. In this Aim, we also attempt to identify additional AtlA-associated components, enhancing our understanding of the architecture and function of AtlA on the cell surface. And in the Specific Aim 3, we will perform a pilot experiment in a mouse caries model to begin to analyze the in vivo impact of AtlA in S. mutans caries development. Overall, this application manipulates an as yet uncharacterized role of AtlA in S. mutans biofilm formation, and data derived from these proposed studies have a high potential to facilitate the development of innovative therapeutic strategies to treat dental caries, e.g. by interfering with the autolytic pathways necessary for the proper development of cariogenic biofilms. This project is also part of our long-term objective elucidating the molecular basis for biofilm maturation and its underlying mechanisms.

描述（申请人提供）：牙齿表面成熟生物膜的发育是口腔细菌生存和发病的重要组成部分。尽管在过去的几年里，口腔生物膜的复杂性已经迅速揭示，但了解细菌如何以一种明确的方式建立成熟的致病生物膜，仍然缺乏，导致难以识别和设计新的抗生物膜治疗靶点。为了达到这个目的，